Metabolomic Profiles, Ideal Cardiovascular Health, and Risk of Heart Failure and Atrial Fibrillation: Insights From the Framingham Heart Study

Yi Li, Ayana Gray, Liying Xue, Melissa G. Farb, Nir Ayalon, Charlotte Andersson, Darae Ko, Emelia J. Benjamin, Daniel Levy, Ramachandran S. Vasan, Martin G. Larson, Jian Rong, Vanessa Xanthakis, Chunyu Liu, Jessica L. Fetterman, Deepa M. Gopal

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


BACKGROUND: The American Heart Association’s framework “ideal cardiovascular health” (CVH) focuses on modifiable risk factors to reduce cardiovascular disease (CVD). Metabolomics provides important pathobiological insights into risk factors and CVD development. We hypothesized that metabolomic signatures associate with CVH status, and that metabolites, at least partially, mediate the association of CVH score with atrial fibrillation (AF) and heart failure (HF). METHODS AND RESULTS: We studied 3056 adults in the FHS (Framingham Heart Study) cohort to evaluate CVH score and incident outcomes of AF and HF. Metabolomics data were available in 2059 participants; mediation analysis was performed to evaluate the mediation of metabolites in the association of CVH score and incident AF and HF. In the smaller cohort (mean age, 54 years; 53% women), CVH score was associated with 144 metabolites, with 64 metabolites shared across key cardiometa-bolic components (body mass index, blood pressure, and fasting blood glucose) of the CVH score. In mediation analyses, 3 metabolites (glycerol, cholesterol ester 16:1, and phosphatidylcholine 32:1) mediated the association of CVH score with incident AF. Seven metabolites (glycerol, isocitrate, asparagine, glutamine, indole-3-proprionate, phosphatidylcholine C36:4, and lysophosphatidylcholine 18:2), partly mediated the association between CVH score and incident HF in multivariable-adjusted models. CONCLUSIONS: Most metabolites that associated with CVH score were shared the most among 3 cardiometabolic compo-nents. Three main pathways: (1) alanine, glutamine, and glutamate metabolism; (2) citric acid cycle metabolism; and (3) glyc-erolipid metabolism mediated CVH score with HF. Metabolomics provides insights into how ideal CVH status contributes to the development of AF and HF.

Original languageEnglish (US)
Article numbere028022
JournalJournal of the American Heart Association
Issue number12
StatePublished - Jun 20 2023


  • atrial fibrillation
  • CVH score
  • heart failure
  • mediation analysis
  • metabolomics

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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